Double-Blind Study

Definition/Introduction

A clinical research study or a clinical trial is an experiment or observation performed on human subjects to generate data on the safety and efficacy of various biomedical and behavioral interventions.[1]

Blinding or masking refers to the withholding of information regarding treatment allocation from one or more participants in a clinical research study. It is an essential methodological feature of clinical studies that help maximize the validity of the research results.[2]

Issues of Concern

Blinding covers any of the numerous participants of the clinical trial, e.g., researchers, subjects, technicians, and data analysts. Single-, double-, and triple-blinding are commonly used blinding strategies in clinical research. A single-blind study masks the subjects from knowing which study treatment if any, they are receiving. A double-blind study blinds both the subjects as well as the researchers to the treatment allocation. Triple-blinding involves withholding this information from the patients, researchers, as well as the data analysts.Randomized, double-blind placebo-controlled trials involve the random placement of participants into two groups; an experimental group, that receives the investigational treatment, and a control group, that acquires a placebo. Neither the researchers nor the study subjects know who is getting the experimental treatment and who is getting a placebo. This type of clinical study is considered to be the gold standard for the validation of treatment interventions.[3]

Unfortunately, blinding is not possible to achieve in all clinical trials. For example, the method of drug delivery may not be amenable to blinding. An excellent clinical protocol may help ensure that within the ethical and practical constraints, blinding is achieved as effectively as possible.

Clinical Significance

Bias refers to a deviation from the truth in the collection, analysis, interpretation, or publication of data, which can lead to false conclusions. Poor blinding of a clinical research study may lead to bias that may result in inflated effect size and increase the risk of type I error. Even a small error in blinding may lead to a statistically significant result without the presence of any real difference between the study groups.[4]

By keeping both the researchers and the subjects blinded to treatment allocation, a double-blinded study can prevent the researchers from treating the study groups differently. The double-blinded study minimizes the risk of various types of biases, such as observer bias or confirmation bias, which may influence the results of the investigation.[5][6] It may also help avoid the occurrence of a disproportionately large placebo effect in the patients involved in the study.[3]

Unblinding may occur during any portion of the blinded clinical trial. Unblinding that occurs before the conclusion of a trial may be a source of bias that the study should document and report. It is the responsibility of all the healthcare professionals involved in a clinical trial, such as physicians, nurses, pharmacists, technicians, and data analysts, to maintain blinding as effectively as possible during the trial, and to report any premature unblinding.[7]